Receptors for the neurotransmitter acetylcholine have been divided into muscarinic and nicotinic. The muscarinic acetylcholine receptors are further divided into pharmacological subtypes M1, M2, M3, and M4. Recently five different muscarinic acetylcholine receptor proteins have been identified (m1, m2, m3, m4, m5). Through use of selective antibodies, the proportion of each of the molecular receptors in each of the brain region has been determined. A post-mortem study of acetylcholine binding sites in Alzheimer's disease, revealed an increase in M1 density in the striatal area of the brain and a decrease in the M2 density in frontal and temporal cortices and hippocampus. This has led to the theory that Alzheimer's disease is a function of the loss of presynaptic M2 receptor function. The M3 subtype is present in the parotid gland and has been shown to be 93% m3. Thus the m3 receptor may be important in the etiology and treatment of salivary disorders such as Sjogren's Syndrome. R-Quinuclidinyl-R-iodobenzilate (R,R-IQNB), a muscarinic antagonist has previously been labeled with 1-123 and 1-125 as an agent for in vitro assays as well as in vivo imaging with single photon emission computed tomography. The absolute configuration at the two chiral centers effects the binding affinity and the pharmacokinetics. The goal of this project is to prepare fluorine containing agonists or antagonists which may be labeled with F-18 for imaging by positron emission tomography (PET). We have developed a stereoselective synthesis of fluoroalkyl QNB analogs and prepared fluoropropyl, fluoroethyl, and fluoromethyl analogs. The in vitro and in vivo properties of these fluoroalkyl QNB analogs was evaluated. In addition, we have prepared fluoro analogs of a class of agonists based on the chemical structure thiadiazole tetrahydropyridine. An F-18 analog has been prepared for in vivo studies in rodents. This analog appears to be m2 selective in vivo.